Synthesis and structure of selected quaternary N-(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-d,l-ribitol-5-yl)ammonium salts

Skorupa, Eugenia; Dmochowska, Barbara; Pellowska-Januszek, Lucyna; Wojnowski, W.; Chojnacki, Jarosław; Wiśniewski, Andrzej

doi:10.1016/j.carres.2004.06.025

Cited by 14 publications

(7 citation statements)

References 17 publications

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“…However, deprotection of 16 with acetic acid failed after multiple attempts, as both the 5- O -trityl and 2-3- O -isopropylidene protecting groups were cleaved, leading to the undesired fully deprotected 1-deoxyribose or to complex mixtures. Using the alternative deprotection of 16 with formic acid in diethylether32 afforded compound 17 (32%) 33. Phosphitylation and subsequent oxidation of 17 with di- tert -butyl N , N -diisopropylphosphoramidite gave the phosphate derivative 18 (41%).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Terminal Ribose Analogues of Adenosine 5′-Diphosphate Ribose as Probes for the Transient Receptor Potential Cation Channel TRPM2

et al. 2019

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TRPM2 (transient receptor potential cation channel, subfamily M, member 2) is a nonselective cation channel involved in the response to oxidative stress and in inflammation. Its role in autoimmune and neurodegenerative diseases makes it an attractive pharmacological target. Binding of the nucleotide adenosine 5′-diphosphate ribose (ADPR) to the cytosolic NUDT9 homology (NUDT9H) domain activates the channel. A detailed understanding of how ADPR interacts with the TRPM2 ligand binding domain is lacking, hampering the rational design of modulators, but the terminal ribose of ADPR is known to be essential for activation. To study its role in more detail, we designed synthetic routes to novel analogues of ADPR and 2′-deoxy-ADPR that were modified only by removal of a single hydroxyl group from the terminal ribose. The ADPR analogues were obtained by coupling nucleoside phosphorimidazolides to deoxysugar phosphates. The corresponding C2″-based analogues proved to be unstable. The C1″- and C3″-ADPR analogues were evaluated electrophysiologically by patch-clamp in TRPM2-expressing HEK293 cells. In addition, a compound with all hydroxyl groups of the terminal ribose blocked as its 1″-β-O-methyl-2″,3″-O-isopropylidene derivative was evaluated. Removal of either C1″ or C3″ hydroxyl groups from ADPR resulted in loss of agonist activity. Both these modifications and blocking all three hydroxyl groups resulted in TRPM2 antagonists. Our results demonstrate the critical role of these hydroxyl groups in channel activation.

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Section: Resultsmentioning

confidence: 99%

Synthesis of Terminal Ribose Analogues of Adenosine 5′-Diphosphate Ribose as Probes for the Transient Receptor Potential Cation Channel TRPM2

et al. 2019

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“…It can be stated that the yields for the syntheses of compounds 4 and 5 were very similar. In syntheses described in our previous papers, 36,37 the presence of the methyl substituent at the C-2 position of the pyridine ring resulted in a reduction in the yield of the salt-forming reaction. We have always interpreted this as an effect of the steric hindrance of the methyl group.…”

Section: Chemistrymentioning

confidence: 92%

Efficient synthesis and antifungal investigation of nucleosides’ quaternaryammonium salt derivatives

Dmochowska¹,

Pellowska-Januszek²,

Samaszko-Fiertek³

et al. 2019

Turk J Chem

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Quaternary ammonium salts are a group of compounds with diverse biological properties, the most important of which are their antiviral, antibacterial, and antifungal activities. The quaternization reactions of 5'-O-tosyl derivatives of uridine and thymidine with triethylamine, trimethylamine, 4-(N , N-dimethylamino)pyridine, 2-methylpyridine, and pyridine are described in this article. Two of the synthesized compounds are exceptional because they are first of this type that demonstrate concentration-dependent antifungal in vitro activity against two species of the genus Candida in minimal YNB-SG medium. The experimental results have been extended by adding full atom molecular dynamics simulations and substrates and products energies evaluation.

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“…It came as no surprise to us that the lowest performance was obtained in the case of N-((methyl 2,3-O-isopropylidene-β-D-ribofuranoside)-5-yl)triethylammonium tosylate (4b) ( Table 1) [30]. Such results are expected to be caused by the large steric hindrance of the nitrogen atom in the amine molecule and, thus, the difficult substitution of the terminal O-tosyl group.…”

Section: Synthesis Of 4b-4k 6a-6f and 6i And 8b-8d And 8fmentioning

confidence: 99%

The Quaternization Reaction of 5-O-Sulfonates of Methyl 2,3-o-Isopropylidene-β-D-Ribofuranoside with Selected Heterocyclic and Aliphatic Amines

et al. 2020

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The synthesis of N-((methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside)-5-yl)ammonium salts are presented. To determine the effect of the nucleophile type and outgoing group on the quaternization reaction, selected aliphatic and heterocyclic aromatic amines reacted with: methyl 2,3-O-isopropylidene-5-O-tosyl-β-D-ribofuranoside or methyl 2,3-O-isopropylidene-5-O-mesyl-β-D-ribofuranoside or methyl 2,3-O-isopropylidene-5-O-triflyl-β-D-ribofuranoside were performed on a micro scale. High-resolution 1H- and 13C-NMR spectral data for all new compounds were recorded. Additionally, the single-crystal X-ray diffraction analysis for methyl 2,3-O-isopropylidene-5-O-mesyl-β-D-ribofuranoside and selected in silico interaction models are reported.

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Synthesis and structure of selected quaternary N-(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-d,l-ribitol-5-yl)ammonium salts

Cited by 14 publications

References 17 publications

Synthesis of Terminal Ribose Analogues of Adenosine 5′-Diphosphate Ribose as Probes for the Transient Receptor Potential Cation Channel TRPM2

Synthesis of Terminal Ribose Analogues of Adenosine 5′-Diphosphate Ribose as Probes for the Transient Receptor Potential Cation Channel TRPM2

Efficient synthesis and antifungal investigation of nucleosides’ quaternaryammonium salt derivatives

The Quaternization Reaction of 5-O-Sulfonates of Methyl 2,3-o-Isopropylidene-β-D-Ribofuranoside with Selected Heterocyclic and Aliphatic Amines

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